Dose-finding study of docetaxel, oxaliplatin, and S-1 for patients with advanced gastric cancer

Purpose  To determine the maximum tolerated dose (MTD), recommended dose (RD), and activity of combined docetaxel, oxaliplatin, and S-1 (DOS) chemotherapy on metastatic gastric cancer. Patients and methods  Docetaxel and oxaliplatin were administered intravenously on day 1 and S-1 was administered orally on days 1–14 of every 21-day cycle. The doses of docetaxel/oxaliplatin/S-1 in the phase I study were level −1A, 52.5/80/60 mg/m²; level −1B, 52.5/80/80 mg/m²; level 1A, 52.5/105/80 mg/m²; level 1B, 52.5/130/80 mg/m²; level 2A, 60/105/80 mg/m²; level 2B, 60/130/80 mg/m²; level 3A, 67.5/105/80 mg/m²; level 3B, 67.5/130/80 mg/m²; level 4A, 75/105/80 mg/m²; level 4B, 75/130/80 mg/m². Results  Nine patients were enrolled. One of six patients at level 1A and two of three patients at level 1B developed dose-limiting toxicity (febrile neutropenia) during the initial two cycles. Therefore, the doses used at levels 1B and 1A were defined as the MTD and RD, respectively. All patients were evaluated for toxicity and response. Six partial responses were noted, and the overall response rate was 67%. Conclusion  The RD of the DOS regimen in patients with advanced gastric cancer was docetaxel 52.5 mg/m² and oxaliplatin 105 mg/m² on day 1 and S-1 80 mg/m² on days 1–14 of every 21-day cycle. A phase II study using the RD is currently underway.     

多西他赛注射液治疗晚期非小细胞肺癌和乳腺癌的随机对照临床研究

目的：观察福州三先药物研究所和南京振华医药科技开发有限公司联合开发的多西他赛注射液治疗晚期非小细胞肺癌和乳腺癌的疗效和毒性。方法：随机入组患者共220例,其中试验组111例,对照组109例。试验组接受新开发的多西他赛注射液,对照组应用艾素。两组非小细胞肺癌采用．rP方案：多西他赛注射液70mg／m^2,第1天,顺铂70mg／m^2,第2天。乳腺癌患者可采用上述的联合方案,也可选用多西他赛单药治疗,100mg／m^2,第1天。所有治疗均每3周重复1次。结果：试验组和对照组治疗晚期非小细胞肺癌／乳腺癌可评价病例共200例,其中试验组100例（肺癌49例,乳腺癌51例）,对照组100例（肺癌48例,乳腺癌52例）,总缓解率分别为31．00％（肺癌28．57％,乳腺癌33．33％）和32．00％（肺癌25．00％,乳腺癌38．46％）,两组比较均无统计学差异（P〉0．05）。试验组和对照组发生与化疗药物相关的毒副反应总发生率分别为93．64％和92．66％,其中Ⅲ～Ⅳ度发生率分别为75．45％和76．15％,两组比较亦均无统计学差异（P〉0．05）。主要毒副反应有白细胞下降、呕吐、肌肉酸痛、腹泻、发热、感染等。结论：新研发的多西他赛注射液治疗晚期非小细胞肺癌和乳腺癌安全有效。     

两种国产多西紫杉醇治疗晚期乳腺癌的随机对照临床研究

背景与目的:两种国产多西紫杉醇化学结构相同,临床前研究显示,它们具有相同的药理作用和毒性。试验用多西紫杉醇经SDA审查后批准作为Ⅳ类新药进行临床研究,本实验旨在评价两种国产多西紫杉醇治疗晚期乳腺癌的疗效和耐受性。方法:采用多中心随机对照研究,患者在接受地塞米松预处理后给予其中一种国产多西紫杉醇75mg/m2,1h静脉输注,每3周为一个疗程,至少接受2个疗程化疗。治疗后评价疗效。结果:共67例患者入组,试验组33例,对照组34例。试验组可评价疗效31例,其中完全缓解(completeremission,CR)1例,部分缓解(partialremission,PR)9例,疾病稳定(stabledisease,SD)11例,疾病进展(progressivedisease,PD)10例,经确认后的总有效率为22.2%。对照组可评价疗效34例,其中CR1例,PR5例,SD19例,PD9例,经确认后的总有效率为15.15%。两组疗效差异无显著性(P=0.662)。两组随访时间8～28个月,中位随访时间16.5个月。治疗组无进展生存(progression-freelysurvival,FPS)时间2～12个月,中位FPS时间为6.2个月;1年生存率68.5%,2年生存率40.1%。对照组FPS时间为2.3～11个月,中位FPS时间为7.1个月;1年生存率65.2%,2年生存率39.7%。两组FPS和1年、2年生存率均无显著性差异(P值分别为0.102,0.096,0.089)。主要不良反应是骨髓抑制、一过性转氨酶升高、脱发,试验组1例发生严重过敏反应,对照组1例发生全身水肿。结论:试验用多西紫杉醇与国内已上市的同类产品疗效、不良反应相当。     

Phase II study of S‐1 plus leucovorin in patients with metastatic colorectal cancer: Regimen of 1 week on, 1 week off

A phase II study of S‐1 plus leucovorin (LV) given in a 4‐week schedule (2 weeks’ administration followed by 2 weeks’ rest) for patients with untreated metastatic colorectal cancer (mCRC) showed that the combination was effective, but grade 3 toxicities (diarrhea, stomatitis and anorexia) occurred at a relatively high rate. In this phase II study, we evaluated the efficacy and safety of a 2‐week schedule of S‐1 plus LV. Patients with mCRC received oral S‐1 (40–60 mg) and LV (25 mg) twice daily for 1 week, followed by 1 week's rest. Treatment was repeated until disease progression or unacceptable toxicity. The primary endpoint was response rate. The pharmacokinetics of S‐1 and LV in Chinese patients were evaluated on day 1 of the first cycle. Seventy‐three patients were enrolled in Japan and China. Of 71 eligible patients, the response rate was 53.5%, and the disease control rate was 83.1%. Median progression‐free survival and median overall survival were 6.5 and 24.3 months, respectively. The incidences of grade 3 toxicities were diarrhea 8.3%, stomatitis 8.3%, anorexia 2.8% and neutropenia 9.7%. There were no treatment‐related deaths. The pharmacokinetics profiles of S‐1 plus LV in Chinese patients were similar to those in Japanese patients. This 2‐week schedule of S‐1 plus LV showed good efficacy and better tolerability than the 4‐week schedule. This therapy will be the base regimen for mCRC to be added by other cytotoxic or molecular‐targeted drugs. The optimized treatment schedule for S‐1 plus LV was 1 week on and 1 week off.     

Phase I dose escalation study of docetaxel with a fixed dose of S-1 in combination chemotherapy for advanced gastric cancer

Background  The primary objectives of this study were to estimate the maximum-tolerated dose (MTD) of docetaxel in combination with a fixed dose of S-1 and to determine the recommended dose (RD). Patients and methods  Patients with histologically proven gastric carcinoma with metastatic or locally advanced inoperable disease were eligible. Patients received intravenous docetaxel starting at 40 mg/m² (dose level 1), and stepwise dose increases to 50, 60, and 70 mg/m² were planned for successive patient cohorts (dose levels 2, 3, and 4, respectively) over 1 h on day 1 and oral S-1 administered at a fixed dose of 40 mg/m² twice daily on days 1–14, both drugs every 21 days. Results  A total of 13 patients were enrolled into this trial. All three patients at dose level 3 developed dose-limiting toxicities (DLT), and this level was declared to be the MTD. Hence, level 2 (docetaxel 50 mg/m²) was declared to be the RD for the next study. As 9 of the 13 enrolled patients responded to treatment, the overall objective response rate was 69.2% (95% CI, 44.1–94.3%). The median time to progression was 8.38 months (range 1.44–8.51) and the overall survival duration was 9.9 months (range 0.62–11.57). The most common grade 3/4 toxicity of docetaxel plus S-1 was neutropenia, which was tolerable and manageable. Conclusion  This regimen showed encouraging activity and a manageable safety profile in advanced gastric carcinoma and could be used in further randomized studies.     

国产多西紫杉醇治疗晚期非小细胞肺癌的随机对照临床研究

背景与目的：多西紫杉醇已成为临床上治疗晚期非小细胞肺癌的主要药物之一。国外报道单药一线治疗晚期非小细胞肺癌的有效率20％,其主要毒性是骨髓抑制。本研究观察易优瑞康（Euruikang,国产多西紫杉醇）治疗晚期初治非小细胞肺癌的疗效和毒性。方法：共77例患者入组。随机分组,试验组38例,对照组39例。试验组接受易优瑞康75mg／m^2,对照组接受艾素75mg／m^2,1小时输注,两组均联合顺铂70mg／m^2,每3周重复疗程。在多西紫杉醇给药前1天开始口服地塞米松7．5mg,每天2次,连服3天预防过敏反应。所有患者均接受两个疗程以上的化疗。结果：试验组可评价37例,PR15例,SD16例,PD6例,总有效率40．54％。33例4周后再次复查评价,确认有效率为28．95％。对照组可评价疗效37例,PR13例,SD16例,PD8例,总有效率35．14％。34例4周后再次复查评价疗效,确认有效率为27．03％。两组疗效差异无统计学意义。易优瑞康主要的毒副作用为Ⅱ～Ⅲ度骨髓抑制,Ⅰ～Ⅱ度脱发、乏力和消化道反应,未见严重的过敏反应发生。结论：本研究所用的易优瑞康注射液是一种治疗晚期非小细胞肺癌安全有效的药物,与国内已上市的同类产品艾素疗效、毒副作用相当。     

胃癌分子靶向治疗的临床研究进展

分子靶向治疗联合化疗为晚期胃癌治疗带来了新的希望.针对晚期胃癌靶向治疗进行的几个国际多中心随机对照Ⅲ期临床研究,包括ToGA、EXPAND、LOGIC、AVAGAST、REAL3、GRANITE-1等确立了胃癌靶向治疗的地位.     

A randomized phase-III trial of docetaxel/capecitabine versus doxorubicin/cyclophosphamide as primary chemotherapy for patients with stage II/III breast cancer

We aimed to determine the efficacies of a non-anthracycline-containing regimen, docetaxel/capecitabine (TX), in comparison with an anthracycline-containing regimen, doxorubicin/cyclophosphamide (AC), as primary chemotherapy for node-positive early stage breast cancer. In this phase-III single center randomized study, we randomized 209 women with axillary node positive, stage II/III breast cancer to receive four cycles of either TX or AC followed by surgery and cross-over to the other treatment as an adjuvant therapy. The primary endpoint was tumor pathologic complete response (pCR). Clinical response rates, toxicity profiles, disease free survival (DFS), and overall survival were secondary objectives. In total, 204 patients had clinical and radiological evaluation of response, and underwent surgery. Compared with AC, TX increased pCR in primary tumors (21% vs. 10%, respectively, P = 0.024) and clinical response (84% vs. 65%, P = 0.003). TX was associated with less nausea and vomiting, but more stomatitis, diarrhea, myalgia, and skin/nail changes than AC. With a median follow-up of 37 months, there was no significant difference in DFS by treatment groups (P = 0.932). Fewer patients developed recurrence who achieved pCR in lymph node (LN) (P = 0.025; hazard ratio, 0.189; 95% CI, 0.044-0.815) in the multivariate analysis. TX showed superior efficacies to AC with increased pathologic and clinical complete response rates. Although these findings did not translate into a gain in DFS, the patients who achieved pCR in LN developed significantly less recurrence.     

A Phase II multi-institutional trial of chemoradiation using weekly docetaxel and erythropoietin for high-risk postoperative head and neck cancer patients

PURPOSE: To determine efficacy and toxicities of postoperative concurrent chemoradiation using docetaxel in high-risk head and neck cancer. METHODS AND MATERIALS: High-risk patients were enrolled 2-8 weeks after surgery. Treatment included 60 Gy for 6 weeks with weekly docetaxel 25 mg/m(2) and erythropoietin alpha 40,000 U for hemoglobin < or =12 g/dL. Primary endpoints included locoregional control (LC), disease-free survival (DFS), and patterns of failure (POF). Secondary endpoints were toxicity and quality of life. RESULTS: Eighteen patients were enrolled (14 male, 4 female), aged 24-70 years (median, 55 years). Primary site included oropharynx = 7, oral cavity = 8, hypopharynx = 1, and larynx = 2. Pathologic American Joint Committee on Cancer Stage was III = 3 patients, IV = 15 patients. High-risk eligibility included > or =2 positive lymph nodes = 13, extracapsular extension = 10, positive margins = 8 (11 patients with two or more risk factors). Docetaxel was reduced to 20 mg/m(2)/week after 5 patients had prolonged Grade 3 or higher mucositis. Overall, number of doses delivered was 2 of 6 = 1, 3 of 6 = 2, 4 of 6 = 2, 5 of 6 = 4, 6 of 6 = 9 patients. With median follow-up of 30 months (range, 5-66), 10 (56%) patients are alive and have no evidence of disease (NED); POF: three local recurrences (two with distant) and 1 distant only. One-year survival was 76%, median PFS and DFS had not been reached. Three-year LC was 82%. No Grade 3 or higher late toxicities were observed, although a few cases of prolonged mucositis and taste loss (>3 months) were seen, particularly at 25 mg/m(2)/week. CONCLUSION: Postoperative radiation therapy with weekly docetaxel 20 or 25 mg/m(2)/week for high-risk postoperative head and neck cancer caused intolerable mucosal toxicity, prompting early study termination. Further studies should consider 15 mg/m(2). Actuarial 3-year LC is 82%, similar to cisplatin-based chemoradiation regimens. Distant metastasis remains an important issue requiring additional systemic interventions.     

Combination docetaxel and trastuzumab treatment for patients with her-2-overexpressing metastatic breast cancer: A multicenter, phase-II study

BACKGROUND: Pre-clinical and clinical studies indicate that a combination of docetaxel and trastuzumab may effectively treat patients with human epidermal growth factor receptor-2 (HER-2) overexpressing metastatic breast cancer. We evaluated the efficacy and safety of this combination in a multicenter, open-label phase II study in Japan. METHODS: Women with metastatic breast cancer whose tumors overexpressed HER-2, as assessed by immunohistochemistry and by fluorescence in situ hybridisation, received 2 to 6 cycles of docetaxel (70 mg/m2, every 3 weeks) and trastuzumab (4 mg/kg loading dose, 2 mg/kg weekly thereafter). The primary endpoint was tumor response. Secondary endpoints were time to disease progression and adverse events. RESULTS: Of the 40 women enrolled in the study, 27 (68%) completed 6 cycles of treatment. Three patients discontinued the study before the second cycle. Median follow-up was 20.8 months (range, 0.6 to 30.9 months). The overall response rate was 65% (26/40; 95% CI, 48% to 79%). The median time to progression was 6.8 months (range, 0.6 to 21.2 months). Of the 40 patients, 35 (88%) had grade 3 or 4 leukopenia, and 33 (83%) had grade 3 or 4 neutropenia. Most instances of leukopenia and neutropenia were manageable by reducing the dose of docetaxel or by treatment with granulocyte colony-stimulating factor. In 4 patients, left ventricular ejection fraction decreased by more than 10% from baseline. CONCLUSIONS: The combination of docetaxel and trastuzumab was as effective as reported in other similar studies and was well tolerated in these patients.     

多西他赛联合腹腔热灌注化疗加热疗治疗晚期卵巢癌

目的探讨多西他赛联合腹腔热灌注化疗加热疗治疗晚期卵巢癌患者的临床疗效。方法选取2011年1月至2012年12月收治的80例晚期卵巢癌患者为研究对象,依据随机数字法分为试验组和对照组。对照组给予多西他赛联合腹腔热灌注化疗,试验组在对照组的治疗基础上给予热疗,观察两组患者的临床疗效和不良反应。结果试验组总有效率(82.5%)显著高于对照组总有效率(60.0%),两组差异有统计学意义(P<0.05)。试验组白细胞减少、恶心与呕吐、消化道反应、肝功能损害的发生率均低于对照组,差异均有统计学意义(均P<0.05)。结论应用多西他赛联合腹腔热灌注化疗加热疗治疗晚期卵巢癌可提高临床疗效,不良反应少,治疗安全性高,值得临床应用。     

多西他赛联合顺铂和氟尿嘧啶治疗晚期胃癌疗效观察

目的观察多西他赛联合顺铂、氟尿嘧啶(DCF方案)治疗晚期胃癌的疗效和不良反应。方法采用DCF方案治疗33例晚期胃癌患者。多西他赛75 mg/m2,d1;顺铂75 mg/m2,d1;氟尿嘧啶750 mg/m2,持续静脉滴注,d1~5,3周1个周期,至少2个周期。结果33例晚期胃癌中,完全缓解(CR)0例,部分缓解(PR)18例(54.5%),稳定(SD)8例(24.2%),进展(PD)7例(21.2%)。中位肿瘤进展时间为6.1个月(3.5~11.5个月),中位总生存期为11.2个月(6.0~14.5个月)。最常见的不良反应为骨髓抑制、消化道反应及可逆性体液潴留,不良反应多为Ⅰ~Ⅱ度,无Ⅳ度不良反应发生。骨髓抑制以白细胞减少为特点,血小板减少及贫血较轻。消化道反应主要表现为恶心呕吐、腹泻、便秘,无Ⅳ度腹泻发生。无治疗相关性死亡。结论DCF方案是治疗晚期胃癌安全有效的化疗方案。     

Phase II study of docetaxel and cisplatin in patients with previously untreated metastatic non-small-cell lung cancer

Background. This phase II study was designed to determine the toxicity and efficacy of a low dose of docetaxel plus a standard dose of cisplatin for patients with metastatic non-small-cell lung cancer (NSCLC). Methods. Eligibility criteria included metastatic disease (stage IV) of NSCLC and a performance status (PS) of 0-2. Cisplatin 80 mg/m² was given i.v. on day 1 and docetaxel 60 mg/m² was given i.v. on day 1. Treatment was repeated every 3 to 4 weeks. Results. Forty-five patients were enrolled in the study, and the median age was 63 years. Forty-two patients (93%) had a PS of 0-1 and 38 (84%) received two to four courses of chemotherapy. The principal toxicity was neutropenia, and grade 3/4 occurred in 36%/49%. Other hematologic toxicities were mild. Of the 45 patients, subsequent chemotherapy was delayed due to toxicities in only 5 patients (11%), and dose modifications were needed in only 3 patients (7%). There were no treatment-related deaths. Non-hematological toxicities were relatively mild. Allergy (2%), skin rash (11%), edema (9%), and neuropathy (9%) occurred infrequently, and all were grade 1 toxicity. Of the 45 patients, 19 showed partial response, giving a response rate of 42%. The median survival time was 43.3 weeks, and the 1-year survival rate of all patients was 38.7%. Conclusion. This cisplatin/docetaxel combination chemotherapy is an active and non-toxic regimen in patients with metastatic NSCLC, a result which suggests that the combination may be suitable for randomized controlled trials. Received: February 24, 2000 / Accepted: June 2, 2000     

奥沙利铂联合替吉奥或多西他赛治疗进展期胃癌的临床疗效分析

目的：比较奥沙利铂联合多西他赛或替吉奥治疗进展期胃癌（AGC）的疗效及安全性。方法选取2011年4月—2013年1月在青海省第五人民医院住院的 AGC 患者共62例,采用随机数字表法将患者随机分为两组,A 组31例接受奥沙利铂联合替吉奥方案,B 组31例接受奥沙利铂联合多西他赛方案;比较两组反应率（RR）、疾病控制率（DCR）、疾病无进展时间、总生存时间和不良反应。结果A 组 RR、DCR、中位疾病无进展时间（mPFS）、中位生存时间（mOS）分别为48．4％、67．7％、5．4个月、9．0个月;B 组相应为54．8％、77．4％、6．2个月、9．8个月,差异均无统计学意义（χ2＝0．26,P ＝0．711;χ2＝0．73,P ＝0．393;χ2＝0．51,P ＝0．473;χ2＝0．03,P ＝0．829）。A 组Ⅰ～Ⅱ级外周神经毒性（9．7％∶22．6％）及恶心呕吐发生率（12．9％∶32．3％）均低于 B 组（χ2＝5．78,P ＝0．002;χ2＝4．63,P ＝0．016）。结论两种化疗方案治疗 AGC 的疗效相当,奥沙利铂联合替吉奥方案可作为进展期胃癌的一种化疗方案,且在耐受性方面优于奥沙利铂联合多西他赛方案。     

ERCC1 Asn118Asn polymorphism as predictor for cancer response to oxaliplatin-based chemotherapy in patients with advanced colorectal cancer

Objective: To assess whether the polymorphism of ERCC1 Asn118Asn (C→T) had effects on cancer response to chemotherapy and outcome in Chinese patients treated with oxaliplatin as first-line chemotherapy regimen for advanced colorectal cancer.Methods: ERCC1 Asn118Asn polymorphism was analyzed in 99 patients with stages Ⅲ and Ⅳ advanced colorectal cancer treated with oxaliplatin-based chemotherapy.For all of the patients, ERCC1 Asn118Asn genotype was analyzed for associations with treatment response and time to disease progress (TTP).Results: The allele frequencies of the ERCC1 gene codon 118 were C/C 50.51% (50/99), C/T 41.41% (41/99), T/T 8.08% (8/99), respectively.Patients with C/C genotype showed higher response rate than those with C/T T/T (OR = 3.764, 95% CI: 1.310-10.813).The median TTP of all patients was 7 months (95% CI: 5.569-8.431).Patients with C/C genotype showed a median TTP of 10 months (95% CI:8.924-11.076), which was longer than 5 months (95% CI: 4.424-5.576) in patients with C/T T/T genotypes.Conclusion:Our results showed a link between ERCC1 Asn118Asn genetic polymorphism and cancer response to oxaliplatin-based chemotherapy and time to disease progress in Chinese patients with advanced colorectal cancer.ERCC1 Asn118Asn genotyping may be of predictive benefit in selecting treatment regimen for advanced colorectal cancer.     

TCF方案治疗进展期胃癌的临床观察

目的观察多西紫杉醇(TXT)联合氟尿嘧啶(5-Fu)持续静脉泵入及低剂量顺铂(DDP)组成的TCF方案治疗进展期胃癌的客观有效率(RR)、毒性反应及生存期。方法全组36例患者均经组织病理学证实。治疗前有可评价的客观指标。其中合并肺转移11例,肝转移12例,腹腔转移7例,腹壁转移5例,骨转移4例。TCF方案应用如下:TXT 60 mg/m2,ivdrip,d1;CF 100~200 mg/m2,iv drip,d1~5,于5-Fu之前用药;5-Fu 500 mg,ivdrip,d1;5-Fu 2~3 g/m2,civ,120 h;DDP20~30 mg/m2,iv drip,d3~5。每21 d重复。结果全组36例均可评价疗效,CR 3例,PR 19例,SD6例,PD 8例,总有效率为61.1%。中位生存期(MST)13个月。主要毒性反应是粒细胞下降、消化道反应和脱发。结论TCF方案治疗进展期胃癌客观疗效肯定,毒副反应轻,患者耐受性良好,可以广泛地应用于临床。     

替吉奥联合胸腹腔注药治疗老年晚期胃癌患者胸腹腔积液

目的 观察替吉奥联合胸腹腔注药治疗老年胃癌患者合并恶性胸腹腔积液的近期疗效和患者不良反应.方法 回顾性分析46例老年胃癌患者治疗情况,46例分为治疗组（22例）和对照组（24例）.两组均行胸腹腔化疗及生物治疗,胸腔或腹腔放置引流管排尽积液,给予顺铂40 ～ 60 mg,香菇多糖4～6mg,地塞米松10 mg注入胸腔或腹腔,1次/周,上述治疗方法连用2～4周.治疗组加替吉奥治疗.浆膜腔注药第1天开始口服替吉奥胶囊,40 ～ 60 rng/m2,2次/d,早晚餐后口服,连服14 d,停药7d,21d为1个周期.比较两组临床近期疗效、生活质量及不良反应.结果 治疗组总有效率为77.3％,对照组为50.0％,两组近期疗效差异有统计学意义（P＜0.05）.治疗组、对照组生活质量改善率分别为86.4％和70.1％,两组差异有统计学意义（P＜0.05）.主要不良反应为消化道反应和骨髓抑制,治疗组恶心、呕吐发生率54.5 ％（12/22）,Ⅲ～Ⅳ级粒细胞减少发生率18.2％（4/22）,均高于对照组,差异有统计学意义（P＜0.05）.无治疗相关的死亡.结论 替吉奥联合顺铂及香菇多糖治疗老年胃癌患者恶性胸腹腔积液,疗效确切,虽然消化道反应及骨髓抑制相对明显,但可以耐受,可改善患者生活质量,延长生存期.     

胃癌患者血清TSGF和IAP测定的临床价值

目的探讨胃癌患者血清肿瘤标志物肿瘤特异性生长因子(TSGF)、免疫抑制酸性蛋白(IAP)测定在诊断及化疗疗效评价中的作用。方法用生化比色定量法及单向免疫扩散法分别测定46例胃癌、50例正常对照的TSGF、IAP值。结果 胃癌患者血清TSGF、IAP值较正常对照明显升高,且与胃癌诊断和化疗疗效密切相关。患者中有远处转移者TSGF、IAP测定值较未转移者明显升高。结论检测血清TSGF、IAP对胃癌的早期诊断、评定化疗疗效、监测复发、判断预后有重要的临床意义。     

XRCC1基因在肿瘤研究中的应用

肿瘤是一种基因病，基因组的稳定与否和肿瘤的发生密切相关。XRCC1基因是一种DNA损伤修复基因，在基因组损伤后的修复过程中发挥作用，对维持基因组的稳定，预防肿瘤的发生有着重要的意义。本文就XRCC1基因的生物学特点，该基因单核苷酸多态性与肿瘤易感性，以及该基因的研究方法等方面进行了文献回顾，为该基因用于肿瘤的预防、诊治提供理论借鉴。     

A phase I pharmacological and biological study of PI-88 and docetaxel in patients with advanced malignancies

Purpose  This study evaluated the safety, toxicity, pharmacological properties and biological activity of PI-88, a heparanase endoglycosidase enzyme inhibitor, with fixed weekly docetaxel in patients with advanced solid malignancies. Experimental design  This was a phase I study to determine the maximal-tolerated dose of escalating doses of PI-88 administered subcutaneously for 4 days per week, along with docetaxel 30 mg/m² given on days 1, 8, 15 of a 28-day schedule. Results  Sixteen patients received a total of 42 courses of therapy. No dose-limiting toxicities were observed despite escalation to the highest planned dose level of PI-88 (250 mg/day). Frequent minor toxicities included fatigue (38%), dysgeusia (28.5%), thrombocytopenia (12%), diarrhea (14%), nausea (12%), and emesis (10%) in the 42 courses. No significant bleeding complications were observed. One patient developed a positive anti-heparin antibody test/serotonin releasing assay with positive anti-platelet factor 4/PI-88 antibodies and grade 1 thrombocytopenia in cycle 5, and was withdrawn from the study without any sequelae. PI-88 plasma concentrations (mirrored by APTT) and urinary elimination were linear and dose-proportional. Docetaxel did not alter the pharmacokinetic (PK) profile of PI-88, nor did PI-88 affect docetaxel PK. No significant relationship was determined between plasma or urine FGF-2, or plasma VEGF levels and PI-88 dose/response. Although no objective responses were observed; 9 of the 15 evaluable patients had stable disease for greater than two cycles of therapy. Conclusion  PI-88 administered at 250 mg/day for 4 days each week for 3 weeks with docetaxel 30 mg/m² on days 1, 8 and 15, every 28 days, was determined to be the recommended dose level for phase II evaluation. This combination was well tolerated without severe toxicities or PK interactions.